Predictive biomarkers for survival benefit with ramucirumab in urothelial cancer in the RANGE trial.

Abstract

The RANGE study (NCT02426125) evaluated ramucirumab (an anti-VEGFR2 monoclonal antibody) in patients with platinum-refractory advanced urothelial carcinoma (UC). Here, we use programmed cell death-ligand 1 (PD-L1) immunohistochemistry (IHC) and transcriptome analysis to evaluate the association of immune and angiogenesis pathways, and molecular subtypes, with overall survival (OS) in UC. Higher PD-L1 IHC and immune pathway scores, but not angiogenesis scores, are associated with greater ramucirumab OS benefit. Additionally, Basal subtypes, which have higher PD-L1 IHC and immune/angiogenesis pathway scores, show greater ramucirumab OS benefit compared to Luminal subtypes, which have relatively lower scores. Multivariable analysis suggests patients from East Asia as having lower immune/angiogenesis signature scores, which correlates with decreased ramucirumab OS benefit. Our data highlight the utility of multiple biomarkers including PD-L1, molecular subtype, and immune phenotype in identifying patients with UC who might derive the greatest benefit from treatment with ramucirumab.

• Authors: Michiel S van der Heijden, Thomas Powles, Daniel Petrylak, Ronald de Wit, Andrea Necchi, Cora N Sternberg, Nobuaki Matsubara, Hiroyuki Nishiyama, Daniel Castellano, Syed A Hussain, Aristotelis Bamias, Georgios Gakis, Jae-Lyun Lee, Scott T Tagawa, Ulka Vaishampayan, Jeanny B Aragon-Ching, Bernie J Eigl, Rebecca R Hozak, Erik R Rasmussen, Meng Summer Xia, Ryan Rhodes, Sameera Wijayawardana, Katherine M Bell-McGuinn, Amit Aggarwal, Alexandra Drakaki
• Journal: Nature communications (Nat Commun) Vol. 13 Issue 1 Pg. 1878 (04 06 2022) ISSN: 2041-1723 [Electronic] England
• PMID: 35388003 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Antibodies, Monoclonal, Humanized
• B7-H1 Antigen
• Biomarkers
• Biomarkers, Tumor

Topics

• Antibodies, Monoclonal, Humanized
• B7-H1 Antigen (analysis)
• Biomarkers
• Biomarkers, Tumor
• Carcinoma, Transitional Cell (pathology)
• Humans
• Urinary Bladder Neoplasms (drug therapy, pathology)
• Ramucirumab